EYA4 inhibitor

EYA4 inhibitor is a novel small-molecule compound that targets the Eyes Absent Homolog 4 (EYA4) protein, a dual-specificity phosphatase. EYA4 is frequently overexpressed in triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC), where it promotes genomic instability by deregulating DNA repair pathways, including Rad51-mediated homologous recombination (HR) and non-homologous end joining (NHEJ). This specific inhibitor functions by disrupting the interaction between EYA4 and single-stranded DNA (ssDNA), which normally acts as a stimulator for EYA4's tyrosine phosphatase activity. By abolishing this enzymatic function, the inhibitor induces DNA double-strand break accumulation, cell cycle defects (such as mitotic failure), and apoptosis. Preclinical studies have demonstrated its efficacy in reducing tumor cell proliferation and enhancing the sensitivity of HR-deficient cancers to DNA-damaging therapies.